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Sitko, A.

Publications and source records attributed to Sitko, A..

2 recordsLinked to original sources

c-Maf and Mafb function combinatorially to establish SGN subtype-specific synaptic properties

Neurons develop diverse synapses that vary in content, morphology, and size. Although transcriptional regulators of neurotransmitter identity have been identified, it remains unclear how other synaptic features are patterned among neuronal subtypes. In the auditory system, glutamatergic synaptic properties vary across three subtypes of spiral ganglion neurons (SGNs) that collectively encode sound information. Here, we show that a combinatorial Maf transcription factor code establishes SGN subtype identity and shapes both shared and subtype-appropriate synaptic properties. We find that c-Maf and Mafb have independent and opposing effects on synaptic morphology and auditory function, while also acting redundantly to impart subtype identities and drive synaptic differentiation needed for normal auditory responses. Additionally, c-Maf and Mafb are expressed at different levels across subtypes and regulate subtype-appropriate gene expression in a dose-dependent manner. Thus, functional diversity of Maf family members enables flexible and robust control of gene expression needed to generate synaptic heterogeneity across neuronal subtypes.

neuroscience↗

Experience-dependent flexibility in a molecularly diverse central-to-peripheral auditory feedback system

Brainstem olivocochlear neurons (OCNs) modulate the earliest stages of auditory processing through feedback projections to the cochlea and have been shown to influence hearing and protect the ear from sound-induced damage through unclear mechanisms. Here, we used single-nucleus sequencing, anatomical reconstructions, and electrophysiology to characterize OCNs during postnatal development and after sound exposure. We identified markers for known OCN subtypes, medial (MOC) and lateral (LOC) OCNs, and show that they express distinct cohorts of physiologically relevant genes that change over development. In addition, we discovered a neuropeptide-enriched LOC subtype that produces Neuropeptide Y along with other neurotransmitters. Throughout the cochlea, both LOC subtypes extend arborizations over wide frequency domains. Moreover, LOC neuropeptide expression is strongly upregulated days after acoustic trauma, potentially providing a sustained protective signal to the cochlea. OCNs are therefore poised to have diffuse, dynamic effects on early auditory processing over timescales ranging from milliseconds to days.

neuroscience↗